Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA.

By K. Karikó, M. Buckstein, Houping Ni, D. Weissman. Immunity, 2005

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The Architecture of SARS-CoV-2 Transcriptome (2020, positive): “The RNA modifications may also contribute to viral survival and immune evasion in infected tissues as the innate immune system is known to be less sensitive to RNAs with nucleoside modification (Karikó et al., 2005).”
Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. (2008, background): “Interestingly, RNA modifications such as those found in mammalian tRNA and rRNA suppress the TLR7-agonist properties, suggesting that these modifications may have evolved to enable discrimination between host and pathogen RNA (Kariko et al., 2005).”
Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses (2015, positive): “Aza thus can demethylate RNA, and unmethylated RNA may activate TLR3 and the interferon response (Karikó et al., 2005).”
mRNA Vaccines in the COVID-19 Pandemic and Beyond. (2021, background): “Indeed, unmodifiedmRNA is sensed by a variety of Toll-like receptors (TLR7,TLR8, TLR3) (60) and other intracellular RNA sensors [e.”
Toll-like receptor function and signaling. (2006, background): “However, PDCs do not express TLR3 and fail to respond to dsRNA.”